The objective of this research is to elucidate and correlate genetic, biochemical, and physiological mechanisms that control human development, differentiation and growth. In particular, we will (1) identify homologous (evolutionarily related) physiological mechanisms and systems, (2) characterize the structural and functional relationships of the proteins involved, (3) trace the evolutionary histories of the proteins and of the mechanisms, and (4) infer the genetic organization that underlies and controls the orderly operation of these mechanisms. We will use a variety of computer-assisted survey and statistical procedures to ascertain homology of protein sequences. Physiological mechanisms are homologous if their component parts are structurally related and if these respective parts function similarly and in the same order with respect to each other. Evolutionary histories constructed from the protein sequences will be correlated with each other and with other data to trace the origin and evolution of the physiological mechanisms, to trace the changes that produced present-day functional differences, to estimate when the genetic duplication that produced related mechanisms occurred, and to determine which aspects of the underlying structure are most well conserved in evolution. From the demonstration of homology between physiological mechanisms will emerge testable hypotheses concerning the underlying genetic organization and the mechanisms that control the orderly events of normal differentiation and growth. Such fundamental knowledge is necessary for the design of rational therapies to correct derangements of normal development.